The long range goal of this proposal is to determine the mechanisms of parathyroid hormone (PTH) and calcitonin (CT) secretion and action. Our specific objectives are to: (1) determine the total amino acid sequence of human PTH, develop improved methods for the isolation and radioiodination of PTH, develop a carboxylregion specific radioimmunoassay of human PTH with general clinical utility and which can be distributed to endocrine laboratories worldwide, and determine the influence of serum concentrations of calcium on the glandular or peripheral metabolism of endogenous PTH; (2) determine the regulatory influences and interactions of calcium, adrenergic and cholinergic neurotransmitters on PTH secretion from normal and abnormal parathyroid tissue in vitro; and (3) determine the physiologic means of modulation of PTH and CT receptor binding and nucleotide cyclase activation in bone and kidney cells in vivo and in vitro. The majority of the methods required to do this research are either ongoing in the principal investigator's laboratory or in the laboratories with which he has had long-term, productive collaborative experience. They include technology and instrumentation for hormone isolation, peptide sequencing, radioimmunoassay of PTH and CT, scanning and transmission electron microscopy, bone cell and parathyroid cell monolayer culture, cyclic nucleotide and adenylate cyclase assays and PTH receptor systems.